SAMe is a water soluble physiologically active substance that plays an important role as a methyl group donor in methylation reaction with various transmethylases within the living body, and is used widely as a therapeutic medication for depression, liver disorder, arthritis and the like, or health foods. The yeast cell contains useful components including 5′-nucleotide, a free amino acid, glutathione, which has antioxidant action and is utilized as a therapeutic medication for liver disorder, β-glucan, which has immune strength enhancement function and intestinal condition improvement function, dietary fibers and the like, and is utilized widely as health foods.
As the conventional production method of SAMe, such a method has been ordinarily used that SAMe is accumulated in cells by fermentative production using a culture medium containing L-methionine as a precursor (see, for example, Non-patent Documents 1 and 2), is extracted and purified by chromatography, and is formed into a stable SAMe salt, such as a salt with sulfuric acid or p-toluenesulfonic acid or a salt with butanedisulfonic acid (see, for example, Non-patent Documents 3 and 4). In the conventional production method, however, large amounts of labor and cost are required for extraction and purification of SAMe accumulated in cells, and it is difficult to produce SAMe, which is important as a therapeutic medication and health foods, at low cost.
An enzymatic synthesis method, which does not require extraction and purification from cells, is known as a substitute method of the fermentative method. Accordingly, SAMe is enzymatically synthesized with adenosine 5′-triphosphate (ATP) and L-methionine as substrates using a SAMe synthesizing enzyme (methionine adenosyltransferase), which is isolated and purified from microorganisms, such as a yeast (see, for example, Patent Document 1 and Non-patent Documents 5 and 10). As compared to the fermentative method, this method has such advantages that SAMe is accumulated in a large amount, and it is not necessary to extract SAMe from the cells, but has various problems, in which preparation of the enzyme is complicated, the resulting enzyme has weak activity, inhibition enzyme activity, such as ATP degradation activity, is necessarily removed, and ATP as the substrate is considerably expensive, and therefore, the method has not been subjected to practical use. According to development of gene engineering in recent years, the enzyme can be conveniently prepared by using cloned SAMe synthesizing enzyme gene (see, for example, Non-patent Documents 6 to 9) to solve the problem in preparation of the enzyme, but other practical problems, such as the use of expensive ATP as the substrate, have not yet been resolved.    [Patent Document 1] JP-A-51-125717    [Non-patent Document 1] Schlenk F., DePalma R. E., J. Biol. Chem., 229, 1037-1050 (1957)    [Non-patent Document 2] Shiozaki S., et al, Agric. Biol. Chem., 53, 3269-3274 (1989)    [Non-patent Document 3] Schlenk F., DePalma R. E., J. Biol. Chem., 229, 1051-1057 (1957)    [Non-patent Document 4] Kusakabe, H., Kuninaka, A., Yoshino, H., Agric. Biol. Chem., 38, 1669-1672 (1974)    [Non-patent Document 5] Mudd S H., Cantoni G L., etal, J. Biol. Chem., 231, 481-492 (1958)    [Non-patent Document 6] Markham G. D., et al, J. Biol. Chem., 255, 9082-9092 (1980)
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